Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001326483 | SCV001517514 | uncertain significance | Birt-Hogg-Dube syndrome | 2021-10-08 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with asparagine at codon 522 of the FLCN protein (p.Thr522Asn). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and asparagine. |
| Ambry Genetics | RCV003169531 | SCV003860937 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-28 | criteria provided, single submitter | clinical testing | The p.T522N variant (also known as c.1565C>A), located in coding exon 11 of the FLCN gene, results from a C to A substitution at nucleotide position 1565. The threonine at codon 522 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |